chr1-169376731-A-T

Position:

• chr1-169376731-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320973.2(BLZF1):​c.220A>T​(p.Met74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLZF1 NM_001320973.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16

Genes affected

BLZF1 (HGNC:1065): (basic leucine zipper nuclear factor 1) Enables ubiquitin protein ligase binding activity. Acts upstream of or within Golgi organization and Golgi to plasma membrane protein transport. Located in Golgi apparatus and nucleoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077834696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLZF1	NM_001320973.2	c.220A>T	p.Met74Leu	missense_variant	3/7	ENST00000367808.8	NP_001307902.1
BLZF1	NM_003666.4	c.220A>T	p.Met74Leu	missense_variant	3/8		NP_003657.1
BLZF1	NM_001320972.2	c.220A>T	p.Met74Leu	missense_variant	3/3		NP_001307901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8	c.220A>T	p.Met74Leu	missense_variant	3/7	1	NM_001320973.2	ENSP00000356782	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.220A>T (p.M74L) alteration is located in exon 3 (coding exon 2) of the BLZF1 gene. This alteration results from a A to T substitution at nucleotide position 220, causing the methionine (M) at amino acid position 74 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.0097	.;T;T;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.67	T;T;.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.078	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;.;.
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.12	N;N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.19	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.0	B;B;B;.;.
Vest4		0.13
MutPred		0.29		Loss of methylation at K77 (P = 0.0628);Loss of methylation at K77 (P = 0.0628);Loss of methylation at K77 (P = 0.0628);Loss of methylation at K77 (P = 0.0628);Loss of methylation at K77 (P = 0.0628);
MVP		0.13
MPC		0.11
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.083
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-169345969;